The chemical name of the active substance mesna is sodium 2-mercaptoethanesulfonate.
Mesna is useful, for example, to protect urinary organs when ifosfamide is used to treat tumors. Mesna has also been used for a long time as a mucolytic agent.
Mesna is a white hygroscopic powder with a characteristic odor. The substance is very sensitive to oxidation and rapidly decomposes to dimesna on contact with oxygen, particularly in a humid atmosphere.
Mesna has hitherto been administered orally, parenterally and as an inhalation. All the dosage forms which have been used in the past have been liquid formulations. For example, the only oral dosage form which has been available has been an aqueous solution. Since mesna is very sensitive to oxidation and reacts in the presence of oxygen to dimesna, which is poorly absorbed, the aqueous solution must be protected against oxygen. For this reason the solution is sealed in glass ampoules. The ampoule has to be opened by the patient just before use. This is a complicated procedure for oral use. What is more, the solution is relatively heavy and needs a great deal of storage space.
The major disadvantage of the orally-administered solution is its very unpleasant taste, with the result that patients are very reluctant to take it, even when flavored. Since patients being treated with cytostatic agents very often tend to suffer from nausea and lack of appetite, the poor taste further impairs compliance. The reasons set out above explain the long-standing need for an agreeable-tasting, stable and individually dosable oral form of administration.
Although mesna is a crystalline powder, all attempts at manufacturing tablets, coated tablets or soft gelatin capsules have hitherto failed. In the case of soft gelatin capsules, embedding mesna in a lipid matrix provided good protection against oxygen and decomposition. Interaction between mesna and the capsule shell, however, repeatedly resulted in the capsules splitting during storage: the capsules were physically unstable. Direct tabletting of the active substance was also unsuccessful because of the high bulk volume of up to 500 ml/100 g.
It was not possible to achieve aqueous granulation of mesna to prepare for tabletting either using conventional pasting or by means of fluidized air bed granulation, since mesna liquefies immediately on contact with water.